Varicella zoster (VZ) virus causes two diseases, varicella and zoster. Varicella, primary infection, occurs when individuals lacking immunity to the virus are exposed. Following varicella, many individuals harbor latent VZ virus. Zoster, secondary infection, results from reactivation of latent VZ virus. Most VZ infections are mild in normal hosts. Immunocompromised patients, however, not only often develop severe VZ infections, but they have an increased incidence of zoster in comparison to the normal population. The aim of this project is to determine why immunocompromised patients tend to develop severe VZ infections and why they are at high risk to manifest reactivation infections due to VZ virus. These studies should provide useful clinical information concerning VZ virus, and they may also contribute significant information concerning viral latency. Humoral and cell mediated immune (CMI) responses to VZ virus will be studied and compared in normal and immunocompromised individuals. Humoral immunity will be measured by sensitive methods, to try to document subclinical as well as clinical reactivation of VZ virus. Shedding of VZ virus by asymptomatic individuals will be looked for. The major thrust of this project, however, will involve of CMI to VZ virus. CMI will be examined by several techniques including T cell and macrophage cytotoxicity, nautral killer cells, antibody dependent cellular cytotoxicity, and lymphocyte transformation. Impaired VZ CMI responses in immunocompromised persons will be correlated with studies of VZ antibody, virus shedding, and development of clinical zoster, to try to identify factors responsible for development of zoster and poor recovery from VZ infections.